Dichloromethane → HCID 21254063, compound

A solution of 676 mg (3.1 mmol) of (±)-3-(4-aminophenyl)-1-ethyl-3-methylpyrrolidin-2-one (from Step 3) in 3.1 mL of concentrated hydrochloric acid was then stirred at about −5° C. in an ice-acetone bath as a solution of 222 mg (3.2 mmol) of sodium nitrite in 1.25 mL of water was added dropwise over about 15 minutes. Stirring was continued at −10° to −5° C. for 45 minutes. The mixture was kept cold and added gradually to a solution of 3.50 g (15.5 mmol) of stannous chloride dihydrate in 2.5 mL of concentrated hydrochloric acid stirred under nitrogen at <0° C. in an ice-acetone bath. After completion of the addition, stirring was continued in the cooling bath for about 30 minutes, and then the mixture was partitioned between 25 mL of ethyl acetate and 4 mL of water. The aqueous layer was washed with an additional 10 mL of ethyl acetate. The combined ethyl acetate fractions were treated cautiously with 25 mL of saturated aqueous sodium carbonate solution, resulting in heavy precipitation and some gas evolution. After dilution with additional ethyl acetate and water, the mixture was filtered. The filtrate was transferred to a separatory funnel, and the ethyl acetate layer was washed with saturated aqueous sodium chloride solution. The organic phase was then dried over magnesium sulfate, filtered, and concentrated in vacuo at room temperature to yield 396 mg (55%) of a viscous, yellow oil; primarily one spot by TLC in 95:5 CH2Cl2. 500 MHz 1H NMR (CDCl3) was consistent with the assigned structure.

1. additionwas added dropwise over about 15 minutes
2. stirringstirred under nitrogen at <0° C. in an ice-acetone bath
3. additionAfter completion of the addition
4. stirringstirring
5. waitwas continued in the cooling bath for about 30 minutes
6. customthe mixture was partitioned between 25 mL of ethyl acetate and 4 mL of water
7. washThe aqueous layer was washed with an additional 10 mL of ethyl acetate
8. additionThe combined ethyl acetate fractions were treated cautiously with 25 mL of saturated aqueous sodium carbonate solution
9. customresulting in heavy precipitation
10. filtrationAfter dilution with additional ethyl acetate and water, the mixture was filtered
11. customThe filtrate was transferred to a separatory funnel
12. washthe ethyl acetate layer was washed with saturated aqueous sodium chloride solution
13. dry with materialThe organic phase was then dried over magnesium sulfate
14. filtrationfiltered
15. concentrationconcentrated in vacuo at room temperature
16. customto yield 396 mg (55%) of a viscous, yellow oil

ORD record

ord-149c3614704941739846325d0aa37614

Source dataset

uspto-grants-2001_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06197975B1